For ADHD, based on a case-control study completed several years ago in a local school district, we are currently preparing a manuscript on ADHD prevalence among elementary school children. Using our epidemiologic case definition, 15.5% of children in grades 1-5 in this school district had ADHD. Though higher than many estimates, ours is based on systematic screening of all children in the schools and so captures children who may not be evaluated in studies involving clinical diagnoses. Future work will address environmental lead exposure as a possible risk factor for ADHD. (see Z01 ES49034;PI Dale Sandler, EB) For ALS, based on a case-control study that we conducted several years ago, we published two manuscripts examining risk factors for ALS: one on occupational exposures and one on polymorphisms in the DNA repair gene XRCC1. We found that construction workers and precision metal worker were at higher risk of ALS and that self-reported exposure to paint strippers, lubricating oils, mineral spirits, and dry cleaning agents also appeared to elevate risk. Our examination of 5 SNP loci in XRCC1 suggested that, for 2 of them, carriers of the variant allele had slightly lower risk of ALS. We have also published a manuscript on the relationship between blood lead levels, biomarkers of bone turnover (indicators of mobilization of lead sequestered in bone), and risk of ALS using the Veterans Administration ALS cohort. We found that a doubling of blood lead level was associated with a 1.9-fold increased risk of ALS after adjustment for age and a measure of bone resorption. (see Z01 ES49005;LI Freya Kamel, EB) We have carried out a case-control study nested within the Agricultural Health Study to examine associations between Parkinson's disease and environmental risk factors, particularly certain pesticide exposures. We are also looking at selected candidate genes as susceptibility factors. This study employs data from the Agricultural Health Study as well as additional questionnaire data and field samples collected expressly for this effort. Analysis of data is underway. Several reports have been presented at national meetings including separate investigations of metal levels in blood, alpha-synuclein gene variants, and OCT2 gene variants as risk or susceptibility factors for Parkinson's disease. We have submitted a manuscript reporting that rotenone and paraquat increase Parkinson's disease risk. A manuscript currently in preparation will report that the risk of Parkinson's disease associated with head injury increases dramatically when the subject carries certain alpha-synuclein genetic variants. We have also worked to combine our data with data from other investigators to study risk factors for Parkinson's disease. Two manuscripts have been submitted: one reporting that genetic variants in the adenosine receptor A2A gene were associated with decreased risk of Parkinson's disease and another reporting that genetic variants in dopamine receptor genes were associated with risk of Parkinson's disease among non-Hispanic whites. (see Z01 ES44007 EB;LI Freya Kamel, EB) Analysis of data from the pilot study of the effects of soy estrogen on neonatal development is complete. We published a finding that salivary cortisol levels are about 40% higher in breast-fed infants than formula-fed infants, contradicting our hypothesis that breast-fed infants would have lower levels this stress hormone because breast-feeding provides more maternal contact, hence less stress, than bottle feeding. A manuscript is in preparation reporting on developmental trajectories through infancy in the size of several putatively estrogen-sensitive organs based on ultrasound imaging. The full-scale study is currently underway. (see Z01 ES44006 EB;PI Walter Rogan, EB)